Erhmann and Grey (J. Nat. Chem. Inst., Vol. 16, 1375-1403) were the first in 1956 to compare the growth of numerous cells and of tissue explants on collagen with cells grown on glass. They observed that in a number of cases, the collagen cells favorably influenced cellular growth.
Then in a more general manner, it was established that the collagen substrates augment growth as well as the differentiation of numerous cells in comparison with other substrates such as glass or plastic. A certain number of cells can be kept alive for a long period of time on a collagen support, and it appears that if the cells are deposited on specific collagens, additional growth factors are not necessary. The adhesion of cells to their substrate, particularly in a collagen matrix, is accomplished thanks to the specific glycoproteins of which the best described is the fibronectine group. It has been shown that certain cells utilizing the glycoproteins are able to adhere to specific collagens. For example, the fibroblasts adhere well to all types of collagens; the chondrocytes attach themselves preferably to Type II collagen and the epithelial and endothelial cells adhere best to Type IV collagen. This unique property leads to the conception of producing coverings of this protein for cellular cultures in vitro.
In addition collagen shows another characteristic which is its low antigenicity; this property is kept to a minimum by cleaving the telopeptides by chemical or enzymatic treatment. That is why this protein in its native state or freed from its telopeptides, will be able to protect synthetic materials, destined to remain in the organism. The antigenic properties of these materials will thus be masked and besides the collargen assists in the establishment of the implant by the cells which will then be able to synthesize new tissue.
Finally the collagen can be an enzyme support. Coulet and Cole, (French Pat. No. 2,235,133) have put into focus a method which permits fixing by covalent bonding of a number of enzymes to collagen, in order to conserve their activities. The efficacy of these fixed enzymes will be a fuction of the surface area of their support with respect to their reactive volumes. When the surface are with respect to the volume will be great, the enzymes will have the greatest efficacy. Thus it is necessary to use as the enzymatic reactors, either the film over which is flowed a very thin layer of the medium or very fine balls placed in a column.
The problem with the fabrication of a collagen film has been solved today (French Pat. Nos. 1,596,789 and 1,595,790) but no one as yet carried out a way to prepare balls or other non-planar supports covered with collagen.
The preparation of these objects or supports covered by collagen is especially of interest in the fields of laboratory work, medicine and industrial chemistry. Until now the preparation was either difficult or onerous or even impossible to make in view of the fact that the collagen solutions utilized for the covering processes are aqueous solutions. The drying of the objects covered with the collagen solution cannot be carried out at a temperature above that of the denaturation of collagen in solution which lies between 30.degree.-40.degree. C. The denaturation results in a considerable diminution of the mechanical properties of the protein, and prevents it from adhering to the object to be covered. At a temperature of less than 30.degree. C. evaporation of the water is very slow as a consequence of the saturing vapor pressure and its affinity for the collagen. This low evaporation velocity renders impossible the obtaining of homogeneous collagen surfaces on a number of objects or supports.
In particular with non-planar objects, the solution flows away and carries the protein to the parts of the support nearest the bottom where an accumulation of material appears.